The long-range goal of this research is to control or regulate the loss of nitrogen and wasting complications associated with diabetes and several other diseases. One aspect of this research involves establishing how hormones, or the lack of certain hormones, influence the process of intracellular protein catabolism in particular tissues. In this proposed project the consequences of chemically-induced diabetes on the rates of degradation of a spectrum of intracellular proteins and two specific enzymes in mouse muscle and liver will be assessed. More specifically, we will determine the effects of alloxan and streptozotocin-induced diabetes on: a) the degradation of long-lived and short-lived proteins separated from supernatant fractions of mouse liver, b) the degradation of one specific enzyme present in liver: glyceraldehyde phosphate dehydrogenase or arginase, and c) intracellular proteases and protease inhibitors in liver. In addition, we plan to determine whether administration of insulin to diabetic mice reverses the effects of diabetes on protein degradation and whether the administration of glucagon to diabetic mice exaggerates the effects of diabetes on protein turnover. The results of the proposed research should establish definitively whether the negative nitrogen balance observed in diabetic animals is due to accelerated protein degradation and whether proteins are affected differentially.